Lipidomic analysis reveals metabolism alteration associated with subclinical carotid atherosclerosis in type 2 diabetes
Abstract Background Disruption of lipid metabolism contributes to increased cardiovascular risk in diabetes. Methods We evaluated the associations between serum lipidomic profile and subclinical carotid atherosclerosis (SCA) in type 1 (T1D) and type 2 (T2D) diabetes, and in subjects without diabetes...
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BMC
2025-04-01
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| Series: | Cardiovascular Diabetology |
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| Online Access: | https://doi.org/10.1186/s12933-025-02701-z |
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| author | Maria Barranco-Altirriba Joana Rossell Núria Alonso Ralf J. M. Weber Emilio Ortega Gavin R. Lloyd Marta Hernandez Oscar Yanes Jordi Capellades Catherine Winder Alexandra Junza Mireia Falguera Josep Franch-Nadal Warwick B. Dunn Alexandre Perera-Lluna Esmeralda Castelblanco Didac Mauricio |
| author_facet | Maria Barranco-Altirriba Joana Rossell Núria Alonso Ralf J. M. Weber Emilio Ortega Gavin R. Lloyd Marta Hernandez Oscar Yanes Jordi Capellades Catherine Winder Alexandra Junza Mireia Falguera Josep Franch-Nadal Warwick B. Dunn Alexandre Perera-Lluna Esmeralda Castelblanco Didac Mauricio |
| author_sort | Maria Barranco-Altirriba |
| collection | DOAJ |
| description | Abstract Background Disruption of lipid metabolism contributes to increased cardiovascular risk in diabetes. Methods We evaluated the associations between serum lipidomic profile and subclinical carotid atherosclerosis (SCA) in type 1 (T1D) and type 2 (T2D) diabetes, and in subjects without diabetes (controls) in a cross-sectional study. All subjects underwent a lipidomic analysis using ultra-high performance liquid chromatography–electrospray ionization tandem mass spectrometry, carotid ultrasound (mode B) to assess SCA, and clinical assessment. Multiple linear regression models were used to assess the association between features and the presence and burden of SCA in subjects with T1D, T2D, and controls separately. Additionally, multiple linear regression models with interaction terms were employed to determine features significantly associated with SCA within risk groups, including smoking habit, hypertension, dyslipidaemia, antiplatelet use and sex. Depending on the population under study, different confounding factors were considered and adjusted for, including sample origin, sex, age, hypertension, dyslipidaemia, body mass index, waist circumference, glycated haemoglobin, glucose levels, smoking habit, diabetes duration, antiplatelet use, and alanine aminotransferase levels. Results A total of 513 subjects (151 T1D, 155 T2D, and 207 non-diabetic control) were included, in whom the percentage with SCA was 48.3%, 49.7%, and 46.9%, respectively. A total of 27 unique lipid species were associated with SCA in subjects with T2D, in former/current smokers with T2D, and in individuals with T2D without dyslipidaemia. Phosphatidylcholines and diacylglycerols were the main SCA-associated lipidic classes. Ten different species of phosphatidylcholines were up-regulated, while 4 phosphatidylcholines containing polyunsaturated fatty acids were down-regulated. One diacylglycerol was down-regulated, while the other 3 were positively associated with SCA in individuals with T2D without dyslipidaemia. We discovered several features significantly associated with SCA in individuals with T1D, but only one sterol could be partially annotated. Conclusions We revealed a significant disruption of lipid metabolism associated with SCA in subjects with T2D, and a larger SCA-associated disruption in former/current smokers with T2D and individuals with T2D who do not undergo lipid-lowering treatment. Graphical abstract |
| format | Article |
| id | doaj-art-2fbe59653e9f49409c48e305871ab7cd |
| institution | OA Journals |
| issn | 1475-2840 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Cardiovascular Diabetology |
| spelling | doaj-art-2fbe59653e9f49409c48e305871ab7cd2025-08-20T01:53:19ZengBMCCardiovascular Diabetology1475-28402025-04-0124111410.1186/s12933-025-02701-zLipidomic analysis reveals metabolism alteration associated with subclinical carotid atherosclerosis in type 2 diabetesMaria Barranco-Altirriba0Joana Rossell1Núria Alonso2Ralf J. M. Weber3Emilio Ortega4Gavin R. Lloyd5Marta Hernandez6Oscar Yanes7Jordi Capellades8Catherine Winder9Alexandra Junza10Mireia Falguera11Josep Franch-Nadal12Warwick B. Dunn13Alexandre Perera-Lluna14Esmeralda Castelblanco15Didac Mauricio16Department of Endocrinology & Nutrition, Hospital de la Santa Creu i Sant PauDepartment of Endocrinology & Nutrition, Hospital de la Santa Creu i Sant PauCIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III (ISCIII)School of Biosciences, University of BirminghamDepartment of Endocrinology and Nutrition, Institut d’Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Hospital ClinicSchool of Biosciences, University of BirminghamDepartment of Endocrinology and Nutrition, Hospital Universitari Arnau de Vilanova i Institut d’investigació biomèdica de Lleida (IRBLleida)CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III (ISCIII)CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III (ISCIII)School of Biosciences, University of BirminghamCIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III (ISCIII)Institute for Biomedical Research Dr. Pifarré Foundation IRB Lleida, University of Lleida and Primary Health Care Centre Tàrrega, Gerència d’Atenció Primaria, Institut Català de la SalutCIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III (ISCIII)School of Biosciences, University of BirminghamB2SLab, Department of Systems Engineering, Automatics, and Industrial Informatics, Universitat Politècnica de CatalunyaDivision of Endocrinology, Metabolism and Lipid Research, Department of Internal Medicine, Washington University School of MedicineDepartment of Endocrinology & Nutrition, Hospital de la Santa Creu i Sant PauAbstract Background Disruption of lipid metabolism contributes to increased cardiovascular risk in diabetes. Methods We evaluated the associations between serum lipidomic profile and subclinical carotid atherosclerosis (SCA) in type 1 (T1D) and type 2 (T2D) diabetes, and in subjects without diabetes (controls) in a cross-sectional study. All subjects underwent a lipidomic analysis using ultra-high performance liquid chromatography–electrospray ionization tandem mass spectrometry, carotid ultrasound (mode B) to assess SCA, and clinical assessment. Multiple linear regression models were used to assess the association between features and the presence and burden of SCA in subjects with T1D, T2D, and controls separately. Additionally, multiple linear regression models with interaction terms were employed to determine features significantly associated with SCA within risk groups, including smoking habit, hypertension, dyslipidaemia, antiplatelet use and sex. Depending on the population under study, different confounding factors were considered and adjusted for, including sample origin, sex, age, hypertension, dyslipidaemia, body mass index, waist circumference, glycated haemoglobin, glucose levels, smoking habit, diabetes duration, antiplatelet use, and alanine aminotransferase levels. Results A total of 513 subjects (151 T1D, 155 T2D, and 207 non-diabetic control) were included, in whom the percentage with SCA was 48.3%, 49.7%, and 46.9%, respectively. A total of 27 unique lipid species were associated with SCA in subjects with T2D, in former/current smokers with T2D, and in individuals with T2D without dyslipidaemia. Phosphatidylcholines and diacylglycerols were the main SCA-associated lipidic classes. Ten different species of phosphatidylcholines were up-regulated, while 4 phosphatidylcholines containing polyunsaturated fatty acids were down-regulated. One diacylglycerol was down-regulated, while the other 3 were positively associated with SCA in individuals with T2D without dyslipidaemia. We discovered several features significantly associated with SCA in individuals with T1D, but only one sterol could be partially annotated. Conclusions We revealed a significant disruption of lipid metabolism associated with SCA in subjects with T2D, and a larger SCA-associated disruption in former/current smokers with T2D and individuals with T2D who do not undergo lipid-lowering treatment. Graphical abstracthttps://doi.org/10.1186/s12933-025-02701-zLipidomic profileType 1 diabetesType 2 diabetesSubclinical carotid atherosclerosisSmoking habit |
| spellingShingle | Maria Barranco-Altirriba Joana Rossell Núria Alonso Ralf J. M. Weber Emilio Ortega Gavin R. Lloyd Marta Hernandez Oscar Yanes Jordi Capellades Catherine Winder Alexandra Junza Mireia Falguera Josep Franch-Nadal Warwick B. Dunn Alexandre Perera-Lluna Esmeralda Castelblanco Didac Mauricio Lipidomic analysis reveals metabolism alteration associated with subclinical carotid atherosclerosis in type 2 diabetes Cardiovascular Diabetology Lipidomic profile Type 1 diabetes Type 2 diabetes Subclinical carotid atherosclerosis Smoking habit |
| title | Lipidomic analysis reveals metabolism alteration associated with subclinical carotid atherosclerosis in type 2 diabetes |
| title_full | Lipidomic analysis reveals metabolism alteration associated with subclinical carotid atherosclerosis in type 2 diabetes |
| title_fullStr | Lipidomic analysis reveals metabolism alteration associated with subclinical carotid atherosclerosis in type 2 diabetes |
| title_full_unstemmed | Lipidomic analysis reveals metabolism alteration associated with subclinical carotid atherosclerosis in type 2 diabetes |
| title_short | Lipidomic analysis reveals metabolism alteration associated with subclinical carotid atherosclerosis in type 2 diabetes |
| title_sort | lipidomic analysis reveals metabolism alteration associated with subclinical carotid atherosclerosis in type 2 diabetes |
| topic | Lipidomic profile Type 1 diabetes Type 2 diabetes Subclinical carotid atherosclerosis Smoking habit |
| url | https://doi.org/10.1186/s12933-025-02701-z |
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